Raquel Moral, Ph.D., a postdoctoral associate in the Fox Chase laboratory of Jose Russo, M.D., presented the results today at the 96th Annual Meeting of the American Association for Cancer Research. Russo is director of the Breast Cancer and the Environment Research Center at Fox Chase. After the morning poster session, he will give an oral presentation on "Estrogens as Carcinogens in the Human Breast."
"Development of breast cancer entails multiple events, in which estrogen appears to play an important role," explained Russo. "Our laboratory has pioneered an in vitro system of cell transformation using estrogens and their metabolites as carcinogenic agents in human breast cells. Our data show that each compartment of the breast has specific differentially expressed genes that provide a genomic signature according to the increasing maturation of the organ.
"Estrogenic agents involved in breast development and possibly in breast cancer may include foreign estrogens, or xenoestrogens, that are used in manufacturing a number of products. The studies of BPA and BBP in young rats were designed to see whether exposure to these hormonally active biological compounds could alter the genomic signatures of the mammary gland during critical stages of development." BPA (bisphenol A) is a synthetic resin used in food packaging, dental sealants and polycarbonate plastic products, which range from CDs and eyeglass lenses to tableware and food and beverage containers, including baby bottles. BBP (n-butyl benzyl phthalate) is a widely used plasticizer used in food wraps and cosmetics.
"In exposing prepubescent female rats to BPA and BBP, our aim was to determine what effects, if any, each compound had on mammary gene expression during at different ages," said Moral.
"Our results showed that exposure to BPA changes the gene expression profile of mammary tissues as a function of age. That is, there was a significant increase in protein production governed by various genes at increasing ages from 21 to 100 days."
These included proteins regulating cell proliferation and differentiation, including tumor-suppressing proteins and a large number of unknown proteins. The exception was decreased expression of the GAD1 gene. It encodes a key enzyme of the GABA-ergic system, which could be involved in hormonal regulation and breast cancer development. GAD1 has consistently been overexpressed in primary breast cancer.
"In contrast, the BBP exposure modified the genomic signature of the mammary gland primarily at 21 days of age and had less effect later," Moral said.
Future studies are needed to determine whether exposure to such xenoestrogens leads to breast cancer in rats and whether these estrogens bring about similar gene alterations in human breast tissue.
In addition to Moral and Russo, Fox Chase co-authors of the BPA and BBP studies include research associate Gabriela A. Balogh, Ph.D., postdoctoral associate Daniel A. Mailo, Ph.D., and research pathologist Irma H. Russo, M.D., as well as Coral Lamartiniere, Ph.D., of the University of Alabama at Birmingham.
Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.
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